NHS基因新变异导致Nance-Horan综合征家系的遗传学研究  

Identification of a novel variant of NHS gene underlying Nance-Horan syndrome

作　　者：陈晓伟[1] 徐佩文[1] 李杰[1] 牛玉萍[1] 康冉冉 高媛[1] Chen Xiaowei;Xu Peiwen;Li Jie;Niu Yuping;Kang Ranran;Gao Yuan(Center for Reproductive Medicine Research,National Research Center for Assisted Reproductive Technology and Reproductive Genetics,Key Laboratory for Reproductive Endocrinology of the Ministry of Education,Shandong University,Jinan,Shandong 250001,China)

机构地区：[1]山东大学生殖医学研究中心,国家辅助生殖与优生工程技术研究中心,生殖内分泌教育部重点实验室,济南250001

出　　处：《中华医学遗传学杂志》2021年第11期1077-1080,共4页Chinese Journal of Medical Genetics

基　　金：国家重点研发计划(2018YFC1004900,2018YFC1003100);山东省自然科学基金(ZR2018PH006,ZR2018MC014)。

摘　　要：目的通过临床表型分析、NHS基因变异检测明确1个Nance-Horan综合征家系的致病原因,为临床诊断提供依据。方法提取先证者及其母亲、外祖父母外周血基因组DNA,进行先天性白内障相关基因的高通量技术测序。根据美国医学遗传学与基因组学学会(American College of Medical Genetics and Genomics,ACMG)遗传变异分类标准与指南判断变异位点的致病性,并进行Sanger测序验证。提取先证者母亲mRNA,用逆转录-PCR检测其转录水平的表达;用短串联重复序列分析其亲缘关系。结果先天性白内障相关基因检测结果显示先证者NHS基因存在c.766dupC(p.Leu256Profs*21)半合子变异,母亲NHS基因存在c.766dupC杂合变异,表型正常的外祖父母及100名表型正常的对照中均未检测到该变异,HGMD等数据库未见该变异的报道。根据ACMG遗传变异分类标准与指南,NHS基因c.766dupC(p.Leu256Profs*21)变异被判定为致病性变异(PVS1+PM2+PM6+PP4)。结论c.766dupC变异可能为该Nance-Horan综合征家系的致病原因。Objective To explore the genetic basis for a pedigree affected with Nance-Horan syndrome.Methods Clinical manifestation of the patients was analyzed.Genomic DNA was extracted from peripheral blood samples of the pedigree members and 100 unrelated healthy controls.A panel of genes for congenital cataract was subjected to next-generation sequencing(NGS),and candidate variant was verified by Sanger sequencing and bioinformatic analysis based on guidelines of American College of Medical Genetics and Genomics(ACMG).mRNA expression was determined by reverse transcriptase-PCR(RT-PCR).Linkage analysis based on short tandem repeats was carried out to confirm the consanguinity.Results A small insertional variant c.766dupC(p.Leu256Profs*21)of the NHS gene was identified in the proband and his affected mother,but not among unaffected members and the 100 healthy controls.The variant was unreported in Human Gene Mutation Database(HGMD)and other databases.Based on the ACMG guideline,the variant is predicted to be pathogenic(PVS1+PM2+PM6+PP4).Conclusion The novel variant c.766dupC of the NHS gene probably underlay the X-linked dominant Nance-Horan syndrome in this pedigree.

关 键 词：先天性白内障 Nance-Horan综合征 NHS基因 致病性变异 X连锁显性遗传 

分 类 号：R596[医药卫生—内科学]